A Growth Factor Heals The Damage To A Preemie's Brain — In Mice

Jan 22, 2014

A naturally occurring substance called epidermal growth factor appears to reverse a type of brain damage that's common in very premature infants.

Repeated doses of EGF led to the complete repair of brain injuries in baby mice that didn't get enough oxygen after birth, researchers reported in the journal Nature. "It was really amazing," says Vittorio Gallo, of Children's National Health System in Washington, D.C. "These mice looked identical to the mice that were not exposed to the injury."

The result is important because each year, tens of thousands of premature babies sustain brain injuries caused by a lack of oxygen, says Joseph Scafidi, a neurologist at Children's and an author of the Nature paper. "Many of the children that I have in my clinic have either cerebral palsy or they have issues with motor skills as a result of what's known as perinatal hypoxia," he says.

This lack of oxygen near the time of birth occurs because children born before the 32nd week of pregnancy tend to have immature lungs and blood cells that are not yet able to deliver enough oxygen to the brain, Scafidi says. So even when they get supplemental oxygen in a neonatal intensive care unit, he says, some brain cells may die.

Previous research had shown that oxygen deprivation often kills specific brain cells called oligodendrocytes. These cells form myelin — the insulation that is wrapped around nerve fibers, Gallo says. "Without myelin, nerve cells do not communicate properly."

Experiments in mice showed that the damaged brain of a newborn mouse actually tries to replace dead or damaged oligodendrocytes, Gallo says. "The problem," he adds, "is that this happens too late."

The researchers thought EGF might start the process sooner, and it did. But the treatment worked only when it was given soon after the injury occurred. That suggests that premature human infants would probably have to be treated within a few weeks of birth, Gallo says.

The EGF was given to mice through the nose — which means it would be easy to administer to a human infant. But use in babies is probably still a long way off, Gallo says, in part because many growth factors are known to encourage the growth of tumors as well as new cells.

So EGF and other growth factors with the potential to repair brain damage may be tried first in adults with multiple sclerosis, a condition that's also caused by a lack of myelin, says Regina Armstrong, of the Uniformed Services University of the Health Sciences in Bethesda. And it's possible, she says, that researchers will find a growth factor treatment that works against both MS and the sort of brain damage found in very premature infants.

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Now, a story about protecting the brains of premature babies. These days, even infants weighing two pounds or less usually survive. But many of these preemies suffer brain damage that leads to disabilities later in life. NPR's Jon Hamilton reports on research that suggests it may be possible to repair that damage.

JON HAMILTON, BYLINE: Joseph Scafidi is a neurologist who knows a lot about what premature birth can do to the brain.

DR. JOSEPH SCAFIDI: Many of the children that I have in my clinic have either cerebral palsy or they have issues with motor skills.

HAMILTON: Or learning disabilities. Scafidi, who works at Children's National Medical System in Washington, D.C., says these problems can be severe or quite subtle.

SCAFIDI: Just watching the way they hold a pen or the way they reach for something or transfer from one hand to another is slightly delayed or different than a child that would have been born full-term.

HAMILTON: Scafidi says these delays and differences are often the result of brain damage caused by a lack of oxygen in the days and weeks after birth. He says this is most common in babies born at least eight weeks early.

SCAFIDI: Children that are born very premature have immature lungs, as well as fetal hemoglobin, which basically affects the way the oxygen is taken in and delivered to the rest of the body, specifically the brain.

HAMILTON: So Scafidi and a team of researchers have been studying how this lack of oxygen harms a developing brain. Vittorio Gallo, another member of the team, says they noticed damage in the brain's so-called white matter, in particular, the death of cells called oligodendrocytes.

DR. VITTORIO GALLO: These cells are fundamentally important because they form myelin. Myelin is the insulation that is wrapped around nerve fibers that allows proper propagation of nerve impulses. Without myelin, nerve cells do not communicate properly.

HAMILTON: Gallo says experiments in mice showed that a damaged newborn brain actually tries to replace the cells that make myelin.

GALLO: The problem is that this happens too late. It happens during development at a time where there is some recovery that is possible, but recovery is not completely normal.

HAMILTON: So the team began looking for a way to start the cell recovery sooner. They thought it might be possible using a substance the body already makes called epidermal growth factor or EGF. Gallo says they gave EGF to baby mice with brain injuries like those seen in very premature infants.

GALLO: It was really amazing to see how these mice not only looked identical to the mice that were not exposed to the injury, but also functional recovery was complete.

HAMILTON: Gallo says the treatment worked in mice only if it was given soon after the injury occurred. So he says premature human infants would probably have to be treated within a few weeks of birth. The EGF was given through the nose, which means it would be easy to administer to an infant. But Gallo says use in babies is probably still a long way off.

In the meantime, scientists are considering a similar treatment for adults with multiple sclerosis. Regina Armstrong at the Uniformed Services University in Bethesda says that's not surprising because both preemies and people with MS have brains without enough myelin insulation around nerve cells.

REGINA ARMSTRONG: What's very similar is that when the cells that normally make the myelin are damaged, you need to effect repair. And to do that, you try to increase the cells that are available for the repair.

HAMILTON: Armstrong says it's possible that scientists will find a growth factor that can repair myelin damage in both people with MS and very premature infants. But there could be a downside to the approach. Armstrong says growth factors able to produce new brain cells also may cause tumors. A report on the research on EGF appears in the journal Nature. Jon Hamilton, NPR News. Transcript provided by NPR, Copyright NPR.